Four Aromatic Sulfates with an Inhibitory Effect against HCV NS3 Helicase from the Crinoid Alloeocomatella polycladia

Idam Hermawan; Atsushi Furuta; Masahiro Higashi; Yoshihisa Fujita; Nobuyoshi Akimitsu; Atsuya Yamashita; Kohji Moriishi; Satoshi Tsuneda; Hidenori Tani; Masamichi Nakakoshi; Masayoshi Tsubuki; Yuji Sekiguchi; Naohiro Noda; Junichi Tanaka

doi:10.3390/md15040117

Four Aromatic Sulfates with an Inhibitory Effect against HCV NS3 Helicase from the Crinoid Alloeocomatella polycladia

Mar Drugs. 2017 Apr 11;15(4):117. doi: 10.3390/md15040117.

Authors

Idam Hermawan¹, Atsushi Furuta^{2

3}, Masahiro Higashi⁴, Yoshihisa Fujita⁵, Nobuyoshi Akimitsu⁶, Atsuya Yamashita⁷, Kohji Moriishi⁸, Satoshi Tsuneda⁹, Hidenori Tani¹⁰, Masamichi Nakakoshi¹¹, Masayoshi Tsubuki¹², Yuji Sekiguchi¹³, Naohiro Noda^{14

15}, Junichi Tanaka¹⁶

Affiliations

¹ Department of Chemistry, Biology and Marine Science, University of the Ryukyus, Nishihara, Okinawa 903-0213, Japan. hermawan_idam@yahoo.com.
² Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan. atsushi.5961@ruri.waseda.jp.
³ Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan. atsushi.5961@ruri.waseda.jp.
⁴ Department of Chemistry, Biology and Marine Science, University of the Ryukyus, Nishihara, Okinawa 903-0213, Japan. higashi@sci.u-ryukyu.ac.jp.
⁵ General Education Center, Okinawa Prefectural University of Arts, 1-4 Shuri Tounokura, Naha, Okinawa 903-8602, Japan. fujitayo@okigei.ac.jp.
⁶ Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. akimitsu@ric.u-tokyo.ac.jp.
⁷ Department of Microbiology, Faculty of Medicine, Graduate School of Interdisciplinary Research, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi 409-3898, Japan. atsuyay@yamanashi.ac.jp.
⁸ Department of Microbiology, Faculty of Medicine, Graduate School of Interdisciplinary Research, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi 409-3898, Japan. kmoriishi@yamanashi.ac.jp.
⁹ Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan. stsuneda@waseda.jp.
¹⁰ Environmental Measurement Research Institute, National Institute of Advanced Industrial Science and Technology, 16-1 Onogawa, Tsukuba, Ibaraki 305-8569, Japan. h.tani@aist.go.jp.
¹¹ Department of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi-shi, Chiba 274-8510, Japan. captain.resonance@gmail.com.
¹² Institute of Medical Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. tsubuki@hoshi.ac.jp.
¹³ Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan. y.sekiguchi@aist.go.jp.
¹⁴ Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan. noda-naohiro@aist.go.jp.
¹⁵ Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan. noda-naohiro@aist.go.jp.
¹⁶ Department of Chemistry, Biology and Marine Science, University of the Ryukyus, Nishihara, Okinawa 903-0213, Japan. jtanaka@sci.u-ryukyu.ac.jp.

Abstract

Bioassay-guided separation of a lipophilic extract of the crinoid Alloeocomatella polycladia, inhibiting the activity of HCV NS3 helicase, yielded two groups of molecules: cholesterol sulfate and four new aromatic sulfates 1-4. The structures of the aromatics were elucidated by spectroscopic analysis in addition to theoretical studies. The aromatic sulfates 1-4 showed moderate inhibition against NS3 helicase with IC₅₀ values of 71, 95, 7, and 5 μM, respectively.

Keywords: NS3 helicase; aromatic sulfates; crinoid; hepatitis C virus (HCV).

MeSH terms

Animals
Antiviral Agents / pharmacology*
Aquatic Organisms / chemistry*
Echinodermata / chemistry*
Hepacivirus / drug effects
RNA Helicases / antagonists & inhibitors*
Sulfates / pharmacology*
Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

Antiviral Agents
Sulfates
Viral Nonstructural Proteins
RNA Helicases